Sunil Devika, Subramaniam Gowtham, Shivanaiah Bhoomika, Tiwari Surya Prakash, Palanisamy Mathivathana, Mariasuresh Modesty Blazy, Vallinayagam Kalaivani, Godara Ganga Jal, Sekar Shwetha, Prabhashankar Arathi Bangalore, Panoskaltsis-Mortari Angela, Sundaresan Nagalingam Ravi, Asirvatham-Jeyaraj Ninitha
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, India.
Cardiovascular and Muscle Research Laboratory, Department of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, 560012, India.
Sci Rep. 2025 Aug 28;15(1):31679. doi: 10.1038/s41598-025-16459-7.
Hypertension can lead to hypertensive heart disease (HHD). Genetically hypertensive Schlager (BPH/2J) mice are valuable models for hypertension research. However, comprehensive sex- and age-related differences in cardiovascular phenotype and HHD progression in this model are currently lacking. Here, we aimed to investigate age- and sex-related changes in blood pressure and cardiac parameters in hypertensive BPH/2J mice and normotensive BPN/3J controls. We utilized adult (4-months) and middle-aged (10-months) mice and non-invasively assessed their blood pressure using a tail cuff method and cardiac parameters through echocardiography. Elevated mean arterial pressure (mmHg ± SD) was observed in both male (BPH/2J: 158 ± 26 versus BPN/3J: 117 ± 9) and female mice (BPH/2J:129 ± 10 versus BPN/3J: 105 ± 14) compared to their normotensive counterparts, starting at adulthood, and persisting through middle-age. Echocardiographic analysis revealed significant cardiac dysfunction in adult hypertensive males, including reductions in ejection fraction (%±SD) (BPH/2J: 41 ± 4 versus BPN/3J: 61 ± 8), and fractional shortening (%±SD) (BPH/2J: 20 ± 3 versus BPN/3J: 32 ± 6), indicating the progression of HHD. In contrast, hypertensive females showed preserved cardiac function despite elevated blood pressure, suggesting sex-based differences in how chronic hypertension affects cardiac health. There was no cardiac fibrosis or pleural effusion in either hypertensive or normotensive mice, regardless of age and sex. In conclusion, this study highlights the BPH/2J mouse as an important model for investigating sex-based cardiovascular differences in the context of hypertension.
高血压可导致高血压性心脏病(HHD)。基因性高血压施拉格(BPH/2J)小鼠是高血压研究的宝贵模型。然而,目前该模型中缺乏关于心血管表型和HHD进展的全面性别和年龄相关差异。在此,我们旨在研究高血压BPH/2J小鼠和正常血压BPN/3J对照小鼠血压和心脏参数的年龄和性别相关变化。我们使用成年(4个月)和中年(10个月)小鼠,并通过尾袖法非侵入性评估其血压,通过超声心动图评估心脏参数。与正常血压的同性别小鼠相比,成年雄性(BPH/2J:158±26 vs BPN/3J:117±9)和雌性小鼠(BPH/2J:129±10 vs BPN/3J:105±14)从成年期开始直至中年期均观察到平均动脉压升高(mmHg±SD)。超声心动图分析显示成年高血压雄性小鼠存在明显的心脏功能障碍,包括射血分数(%±SD)降低(BPH/2J:41±4 vs BPN/3J:61±8)和缩短分数(%±SD)降低(BPH/2J:20±3 vs BPN/3J:32±6),表明HHD进展。相比之下,高血压雌性小鼠尽管血压升高但心脏功能保留,提示慢性高血压影响心脏健康存在性别差异。无论年龄和性别,高血压或正常血压小鼠均未出现心脏纤维化或胸腔积液。总之,本研究强调了BPH/2J小鼠是在高血压背景下研究性别相关心血管差异的重要模型。